Five Undescribed Steroids from Talaromyces Stipitatus and Their Cytotoxic Activities Against Hepatoma Cell Lines

Five undescribed sterol derivatives, (22E,24R)-7 alpha-methoxy-5 alpha,6 alpha-epoxyergosta-8(14),22-diene-3 beta,15 beta-diol, (22E,24R)-5 alpha,6 alpha-epoxyergosta-8(14),22-diene-3 beta,7 beta,15 alpha-triol, (22E,24R)-3 beta,5 alpha-dihydroxy-14 beta,15 beta-epoxyergosta-7,22-diene-6-one, (22E,24R)-6 alpha-methoxy-7 alpha,15 beta-dihydroxyergosta-4,8(14),22-triene-3-one, and (25S)ergosta-7,24(28)-diene-3 beta,4 alpha,6 alpha,26-tetraol were isolated from the extract of Talaromyces stipitatus, along with eight known congeners. This is the first example of a class of ergosterols isolated from T. stipitatus. Their structures with absolute configurations were elucidated based on NMR spectroscopic data, ECD calculations, and X-ray crystallographic analyses. All these compounds were tested for their effects on three hepatoma cell lines including Hep3B, HepG2, and Huh-7. Moreover, (22E,24R)-5 alpha,6 alpha-epoxyergosta-8(14),22-diene-3 beta,7 beta,15 alpha-triol and (22E,24R)-9 alpha,15 alpha-dihydroxyergosta-4,6,8(14),22-tetraen-3-one were further evaluated for their impacts on cell cycle progression and apoptosis due to their pronounced cytotoxicity, to uncover their underlying mechanisms. Our results suggested that their antiproliferative activities were mainly mediated by inducing cell apoptosis.